Inhalation device

ABSTRACT

An inhalation device for delivery of a powdered medicament comprising a suction tube ( 21 ) and one or more doses of powdered medicament. The suction tube ( 21 ) has a distal end ( 28 ) and a proximal end ( 29 ) with an air passage ( 30 ) therethrough, the distal end ( 28 ) having an air inlet and the proximal end ( 29 ) having an air outlet which forms the mouthpiece of the device. The inhalation device further comprises a means for drying air ( 23 ) drawn by a user into the inhalation device prior to contact with the aggregated powdered medicament such that a dose of powdered medicament will be dispersed in dried air for delivery at the proximal end.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is the national phase application under 35 U.S.C. § 371of PCT International Application No. PCT/SE02/00990 which has anInternational filing date of May 21, 2002, which designated SwedishApplication Serial No. 0101825-8, filed May 22, 2001 as priority, thecontents of which are incorporated by reference in their entirety.

TECHNICAL FIELD

The present invention relates to an inhalation device for delivery of apowdered medicament, generally referred to as a dry powder inhaler (DPI)and used for local and systemic administration, particularly in thetreatment of respiratory conditions.

BACKGROUND

Several types of dry powder inhalers are known and in this respectreference should be made to WO 97/40876, WO 98/41256 and WO 92/04069which disclose examples of such inhalers.

WO 97/40876 describes an inhalation device comprising a suction tube andblister pack assembly. The blister pack assembly is in the form of acarrier or support unit which holds the blister pack. The carrier orsupport unit is configured such that the upper surface has a pluralityof holes which sit above the blisters in the blister pack. Accordingly,the distal end of the suction tube can be placed in a blister when theuser needs to inhale the powdered medicament.

WO 98/41256 describes an inhalation device which is known as theTURBUHALER®. This inhalation device has a dosing means which is operatedby twisting a rotatable gripping portion. The twisting action releases adose of powdered medicament into a dosing unit which can then be inhaledby the user.

WO 92/04069 describes an inhalation device which is known as theMONOHALER® delivering only a single dose of powdered medicament. Thepowdered medicament is released by removing sealing foil portions and isthen simply inhaled by the user inhaling through the mouthpiece.

Dry powder inhalers (DPI's) have many advantages over inhalers such aspressurised metered dose inhalers (PMDI's). For example, no propellantsare needed, pure drug administration is possible and they are relativelysimple to operate. However, a disadvantage encountered in dry powderinhalers is their sensitivity to moisture. Some dry powder formulationssuffer negative effects when the humidity in the air inhaled through theinhalation device increases. In particular, the relative humidity (RH)will result in an increase in retention of the powder formulation in theinhalation device. At high relative humidity the water molecules in thehumid air will react with the surface of the particles of the powderformulation during the short time it takes for the incoming inhaled airto move or lift and deaggregate the powder.

SUMMARY

Whilst the powder formulation could be processed, e.g. conditioned toreduce its reaction with water molecules in the humid air, it has beendiscovered through experimentation that one of the most efficient waysto reduce the negative effects of humidity is to dry out the incomingair prior to contact with the aggregated powder formulation so that adose of powdered medicament will be dispersed in dried air forsubsequent inhalation by the user.

The negative effects of humidity occur both in the short term and thelong term. The short term effects are the decrease in aerosol quality,e.g. difficulties with deaggregation of powder (in both spheronized andordered mixtures) and the retention of the powder formulation in theinhalation device. The long term effects arise as a result of physicaland/or chemical degradation of the powder formulation mainly due tocontact with water. For example, water will normally be introduced tothe powder formulation due to handling before and during filling of theinhalation device and during storage by permeation through thepackaging. In the case of multi-dose reservoir-type inhalation devicessuch as the TURBUHALER®, water can also accumulate during each dosedelivery. Clearly, any drying capacity introduced into the inhalationdevice may also be used to keep the powder formulation dry and thusavoid chemical degradation. It would also be possible to fill theinhalation device under humid conditions and then dry the contents afterfilling.

A measure of how effective an inhalation device is can be obtained bymonitoring the fine particle fraction (FPF), i.e. the fraction ofparticles which have an aerodynamic diameter of less than 5 mm. Ingeneral, only fine particles are effective in reaching the part of thebody at which the powder formulation is directed since the largerparticles will not be dispersed properly and will not be able to travelwith the inhaled air to the treatment or absorption zone. The FPF as apercentage of the dose of powder formulation decreases significantly asthe relative humidity (RH) increases. In this respect, reference shouldnow be made to FIG. 1A which is a graphic depiction of the variation ofFPF with increasing RH for a typical moisture sensitive powderformulation. Four different ordered mixtures of powder formulation weremonitored.

The retention of the powder formulation in the inhalation deviceincreases with relative humidity (RH) and this can be seen in FIG. 1Bfor the same four ordered mixtures of powder formulation.

FIG. 1C depicts the increase in chemical degradation after a storageperiod of six months as the relative humidity increases.

The object of the present invention is to overcome the disadvantageswhich arise as a result of humidity in dry powder inhalation devices.

According to the present Invention, there is provided an inhalationdevice for delivery of a powdered medicament comprising a suctionchannel and one or more doses of powdered medicament, the suctionchannel having a distal end and a proximal end with an air passagetherethrough, the distal end having an air inlet and the proximal endhaving an air outlet which forms the mouthpiece of the device, whereinthe inhalation device further comprises a means for drying air drawn bya user into the inhalation device prior to contact with the aggregatedpowdered medicament such that a dose of powdered medicament will bedispersed in dried air for delivery at the proximal end.

Preferably, at least part of the volume of the air drawn by the userinto the inhalation device passes through the means for drying the airprior to contact with the powdered medicament.

Preferably, the means for drying air is located such that the air isdried prior to entering the air inlet.

Preferably, the suction channel is in the form of a suction tube and thepowdered medicament is located outside the suction tube.

Preferably, the powdered medicament is contained in a blister packhaving one or more blisters and the suction tube is constructed suchthat the distal end can penetrate a blister.

Preferably, the inhalation device further comprises a housing having oneor more channels therein for directing air inhaled by the user to theair inlet.

Preferably, the means for drying the air is located between the housingand the air inlet.

Preferably, the housing forms part of the suction tube.

Preferably, the means for drying the air is located within the housing.

Preferably, the means for drying the air is located within the blisterpack.

Preferably, the housing is partly formed by the suction tube and partlyformed by the blister pack.

Preferably, the means for drying the air is located in the blister pack.

Preferably, at least one bypass channel is provided in the mouthpiece tofacilitate inhalation by the user.

Preferably, the suction channel is in the form of a suction tube and thepowdered medicament is located in a cavity in the suction tube and themeans for drying the air is located between the air inlet and thecavity.

DESCRIPTION OF DRAWINGS

Preferred embodiments of the present invention will now be described indetail, by way of example only, with reference to the accompanyingdrawings, in which:

FIG. 1 is a schematic diagram of a first preferred embodiment of aninhalation device according to the present invention;

FIG. 1A is a graphic depiction of the variation of fine particlefraction (FPF) with increasing RH.

FIG. 1B is a graph of powder retention as a function of relativehumidity as dose withdrawal.

FIG. 1C is a graph of chemical degradation after six months storage as afunction of storage relative humidity.

FIG. 2 is a sectional view through the suction tube and blister pack ofthe inhalation device in FIG. 1 before insertion of the suction tubeinto the blister pack;

FIG. 3 is a sectional view through the suction tube and blister pack inFIG. 2 after insertion of the suction tube into the blister pack;

FIG. 4 is a perspective view of a second preferred embodiment of thepresent invention;

FIG. 5 is an exploded view of the elements in FIG. 4;

FIG. 6 is a perspective view of the inhalation device in FIG. 4 whenplaced in a regeneration box;

FIG. 7 is a sectional view through the inhalation device in FIG. 4before insertion of the suction tube into the blister pack;

FIG. 8 is a sectional view through the inhalation device in FIG. 4 afterinsertion of the suction tube into the blister pack;

FIG. 9 is a perspective view of a third preferred embodiment of thepresent invention;

FIG. 10 is an exploded view of the elements in FIG. 9;

FIG. 11 a is a perspective view of the inhalation device in FIG. 9 whenplaced in a regeneration box;

FIG. 11 b is a perspective view of the regeneration box in FIG. 11 awithout the inhalation device;

FIG. 12 is a sectional view of the inhalation device in FIG. 9 afterinsertion of the suction tube into the blister pack;

FIG. 13 is an enlarged view of one of the flaps in the inhalation devicein FIG. 12;

FIG. 14 is a perspective view of a fourth preferred embodiment of thepresent invention;

FIG. 15 is an exploded view of the elements in FIG. 14;

FIG. 16 is a sectional view of the inhalation device in FIG. 14 afterinsertion of the suction tube into the blister pack;

FIG. 17 is a perspective view of a fifth preferred embodiment of thepresent invention;

FIG. 18 is an exploded view of the elements in FIG. 17;

FIG. 19 is a perspective view from below of the suction tube in FIG. 18;

FIG. 20 is a sectional view through the inhalation device in FIG. 17before insertion of the suction tube into the blister pack;

FIG. 21 is a sectional view through the inhalation device in FIG. 17after insertion of the suction tube into the blister pack;

FIG. 22 is a perspective view of a sixth preferred embodiment of thepresent invention;

FIG. 23 is an exploded view of the elements in FIG. 22;

FIG. 24 is a sectional view through the inhalation device in FIG. 22before insertion of the suction tube into the blister pack;

FIG. 25 is a sectional view through the inhalation device in FIG. 22after insertion of the suction tube into the blister pack;

FIG. 26 is a perspective view from below of the suction tube in FIG. 22;

FIG. 27 is a perspective view of a seventh preferred embodiment of thepresent invention;

FIG. 28 is an exploded view of the elements in FIG. 27;

FIG. 29 is a sectional view through the inhalation device in FIG. 27before insertion of the suction tube into the blister pack;

FIG. 30 is a sectional view through the inhalation device in FIG. 27after insertion of the suction tube into the blister pack;

FIG. 31 is a perspective view from below of the suction tube in FIG. 27;

FIG. 32 is a perspective view through an eighth preferred embodiment ofthe present invention;

FIG. 33 is an exploded view of the elements in FIG. 32;

FIG. 34 is a sectional view through the inhalation device in FIG. 32before insertion of the suction tube into the blister pack;

FIG. 35 is sectional view through the inhalation device in FIG. 32 afterinsertion of the suction tube into the blister pack;

FIG. 36 is a perspective view of a ninth preferred embodiment of thepresent invention;

FIG. 37 is an exploded view of the elements in FIG. 36;

FIG. 38 is a sectional view through the inhalation device in FIG. 36before insertion of the suction tube into the blister pack;

FIG. 39 is a sectional view corresponding to FIG. 38 after insertioninto the blister pack.

FIG. 40 is a sectional view through a tenth preferred embodiment of thepresent invention;

FIG. 41 is an exploded view of an eleventh preferred embodiment of thepresent invention;

FIG. 42 is a perspective view of the inhalation device in FIG. 41 whenassembled;

FIG. 43 is a sectional view through the inhalation device in FIG. 41;and,

FIG. 44 is an enlarged view of the distal end of the inhalation devicein FIG. 43.

DETAILED DESCRIPTION

Reference should now be made to FIG. 1 which is a schematicrepresentation of the first preferred embodiment of the inhalationdevice.

The inhalation device comprises a suction tube 1 and a blister pack 2holding several doses of a powdered medicament. When the user inhalesthrough the suction tube 1 air will be drawn through a drying box 3which contains bulk drying agent. The drying box 3 is provided withvalves 4 and 5 which ensure that moisture does not enter the drying box3 when the inhalation device is not in use. Dried air will pass from thedrying box 3 through a hose 6 to the suction tube 1.

When a bulk drying agent is used, the inhalation device can be protectedduring long term storage.e.g. up to 24 months and in some cases evenlonger. It is not a requirement that all air drawn through the dryingbox 3 and into the suction tube 1 is dried. The amount of dryingrequired will vary depending upon how sensitive the powder formulationin the blister pack 2 is and also how sensitive the inhalation device isrequired to be. For example, it may be sufficient to dry only the firstfraction of the air inhaled or only reduce the moisture content ratherthan drying the air completely. In some types of inhalation device, thepowder formulation is completely delivered after only a very short timewith the initial airflow. Accordingly, only the initial airflow needs tobe dried and the remaining airflow can continue without drying until theuser completes the inhalation process.

Typically, there will be sufficient bulk drying agent in drying box 3 todry the air which will be inhaled during emptying of all the blisters inthe blister pack 2.

FIG. 2 is a sectional view through the suction tube 1 in FIG. 1 and oneblister 7 in the blister pack 2 before penetration of the blister 7.

The suction tube 1 comprises a distal end 8 and a proximal end 9 with anair passage 10 therethrough. The distal end 8 forms the air inlet andthe proximal end 9 forms the air outlet which is the mouthpiece of theinhalation device. The distal end 8 comprises a cutting mechanism whichtypically includes a cutting blade 15 a and plunger blades 15 b to pushthe cut blister 7 fully open and ensure that there is a clear passagefor airflow into and out of the cavity 13.

The blister pack 2 comprises a lower base 11 and an upper foil layer 12.The lower base 11 has one or more cavities 13 which hold the powderformulation to be inhaled. The upper foil layer 12 seals the powderformulation within the cavity or cavities 13.

In this embodiment the suction tube 1 comprises a housing 14 around thedistal end 8 which directs dried air flowing through hose 6 to the airinlet in the distal end 8.

When the user has penetrated the blister 7, inhalation from themouthpiece 9 will draw dried air from the drying box 3 through hose 6into the housing 14, down into the cavity 13 and up through the distalend 8 to finally pass through the air passage 10 to the user. Airflowarrows have been added to FIG. 3 to show the direction of airflow.

Preferably, the housing 14 forms an air-tight chamber above the blisterpack 2 to avoid moist air being drawn into contact with the powderformulation in the blister 13. However, the volume within the housing 14should be minimised because the moist air within this volume will comeinto contact with the contents of the cavity 13 on penetration.

The valve 5 is a preferred feature which will prevent moist air frompassing through the suction tube 1 back into the drying box 3. Ifincluded, valve 5 should be placed as close to the suction tube 1 aspossible otherwise, moist air will sit within the length of hose 6between the suction tube 1 and valve 5 which will then pass into thehousing 14 when the user next uses the inhalation device. The valves 4and 5 can be actuated by the user, e.g. mechanical, electrical, magneticor suction operated or by the action of penetrating the blister 7. Servomotors could be used, for example, or the valves could be actuated byusing body heat in combination with shape-memory alloys or bi-metals

Suitable forms of drying agent would be all materials that are able toremove water from air, e.g. by binding water or by reacting with water.Solid materials are preferred but materials in all physical states canbe used. Materials that are nonhazardous and that do not form hazardousproducts are preferred as well as materials that do not change physicalstate. All geometric forms can be used.

The drying material can be used as is or in mixtures. Examples aredesiccant powder in a polymer matrix and desiccant powder on the surfaceof a solid support. Suitable materials are also materials where thematerial as such has no affinity for water but where the surface can bemade hydrophilic by for instance oxidation.

Basically, all materials that have affinity for water may be used asdrying materials. Inorganic examples would be Calcium chloride, Calciumoxide, Calcium sulfate, Copper(II) sulfate, Magnesium oxide, Magnesiumperchlorate, Magnesium sulfate, Potassium carbonate, Sodium sulfate,Calcium hydride, Lithium aluminium hydride, Potassium hydroxide, Sodiumhydroxide, Sodium oxide, Sodium-lead alloy, Phosphor pentoxide,Sulphuric acid, Molecular sieve, Silica gel and Aluminium oxide. Organicexamples would be Carbohydrates, Monosaccarides (e.g. glucose, mannose,fructose, and galactose), Disaccarides (e.g. sucrose, lactose,trehalose), Oligosaccarides (e.g. carrageenan, cellulose), Proteins andLipids.

Other organic materials would be cotton, viscose, starch, paper, silk,wool, and hydrogels (e.g. crosslinked acrylate copolymer).

Suitable mixtures would be polymers (e.g. polypropylene) mixed withdesiccant (e.g. silica or molecular sieve), desiccants (e.g. aluminiumoxide) on a solid support.

FIGS. 4 to 8 depict various views of the second preferred embodiment.The inhalation device comprises a suction tube 21 and a blister pack 22.A drying agent 23 surrounds the suction tube 21 and is held within ahousing 24. The drying agent 23 will typically be capable of drying theair for one or two doses of powder formulation from the blister pack 22.In this embodiment, the blister pack 22 depicted has only a singleblister 25. However, the drying agent 23 can be regenerated by placingthe inhalation device in a drying box 26 (see FIG. 6) which will befilled with a large bulk of drying agent 27 capable of drying the powderin a multi-dose blister pack.

FIGS. 7 and 8 are sectional views before and after penetration of theblister pack 22. The suction tube 21 comprises a distal end 28 and aproximal end 29 with an air passage 30 therethrough. The distal end 28forms the air inlet and the proximal end 29 forms the air outlet whichis the mouthpiece of the inhalation device.

The blister pack 22 comprises a lower base 31 and an upper foil layer32. The lower base 31 has one or more moulded cavities 33 which hold thepowder formulation to be inhaled. The upper foil 32 seals the powderformulation within the cavity or cavities 33.

In this embodiment, the suction tube 21 comprises an open housing 24which surrounds the suction tube 21 in the area of the distal end 28.

When the user has penetrated the blister 25 (see FIG. 8) the housing 24comes to rest on the foil layer 32 above the blister 25 so that when theuser inhales, moist air will be drawn through the upper end 34 of thehousing 24, down through the drying agent 23 (where it is dried),through the lower end 35 of the housing 24 into the cavity 33 and upthrough the distal end 28 of the suction tube 21 into the air passageway30 to the user. The cutting mechanism on the distal end 28 will not bedescribed again in detail since it is substantially identical to that inFIG. 2 and in the further embodiments depicted in FIGS. 9 to 44. Airflowarrows have been added to FIG. 8 to show the direction of airflow.

The drying agent 23 is sufficient for at least one or two inhalations.Although the drying agent 23 is exposed to air at the upper end 34,non-flowing air will be dried slowly so that when the inhalation deviceis not in use exposure to the surrounding air does not affect itnoticeably.

When not in use, and to regenerate the drying agent 23, the inhalationdevice is stored in an air-tight drying box 26 which is partly filledwith a bulk drying agent 27. The drying box 26 must be air-tight toavoid undesirable degradation of the bulk drying agent 27. Preferably,there is sufficient bulk drying agent 27 to regenerate the drying agent23 enough times to empty all the blisters 25 in the blister pack 22.

A third preferred embodiment of the present invention is depicted inFIGS. 9 to 13. The inhalation device comprises a suction tube 41 and ablister pack 42. A drying agent 43 surrounds the suction tube 41 and isheld within a housing 44. This embodiment works in a similar manner tothat depicted in FIGS. 4 to 8 except that the housing 44 is providedwith hinged flaps 56 biased into a closed (horizontal) position by weaksprings 58. The flaps 56 are located at both the upper end 54 and thelower end 55 of the housing 44. When the user inhales the flaps 56 willbe opened and moist air will flow into the housing 44 as indicated bythe airflow arrows in FIG. 12. The moist air will pass through thedrying agent 43, (where it is dried), through the flaps 56 at the lowerend 55 of the housing 44 and into the cavity 53. The dried air will thenlift the powder formulation within the blister 45 in the blister pack 42up through the distal end 48 of the suction tube 41 and through airpassage 50 to the mouthpiece 49. Reference numerals 51 and 52 identifythe lower base and the upper foil respectively of the blister pack 42.

The flaps 56 are open during the entire inhalation procedure by thepressure difference created on suction by the user. As soon asinhalation ceases, the weak spring force will return the flaps 56 to theclosed (horizontal) position. The drying agent 43 has to have a veryfast initial moisture adsorption and there must be a slow migration ofwater within the drying agent once adsorbed. In this way, the initialvolume of moist air which enters housing 44 will be dried but the dryingsurface will saturate very quickly. At this point, no further moisturecan be adsorbed. However, after use the adsorbed water will eventuallyreach equilibrium in the drying agent and the drying surface will onceagain be able to adsorb moisture. Accordingly, a drying box may not berequired because the drying agent 43 naturally regenerates after eachuse and has sufficient capacity to adsorb the moisture involved inemptying a complete blister pack 42. However, if further drying isrequired, the drying box 46 in FIGS. 11 a and 11 b could be used. Theflaps 56 open on contact with three sets of hooks 40 a, 40 b when theinhalation device is returned to the drying box 46 to regenerate thedrying agent 43. Each hook set 40 a, 40 b comprises a sloped guide 40 aand a hook element 40 b. The hook elements 40 b can open three of theflaps 56 which is sufficient to ensure that the drying agent 43 isadequately exposed to the bulk drying agent 47. In a similar manner tothe second embodiment, there should be sufficient bulk drying agent 27to allow the user to empty a complete blister pack 42. The advantages ofthis embodiment over the second embodiment are that the flaps 56 protectthe drying agent 43 when removed from the drying box 46 and that theairflow can be shut off after a specified time or a specified volume ofairflow, e.g. using servo motors. Clearly, the less exposure the dryingagent 43 has to moist air when removed from the drying box 46 beforeinhalation, the less risk there is of the drying agent 43 performinginadequately during inhalation.

A fourth preferred embodiment of the inhalation device described withreference to FIGS. 14 to 16 is provided with bypass inlets 57 at thelower end 55 of the housing 44. In all other respects, the inhalationdevice in FIGS. 14 to 16 is identical to the third embodiment depictedin FIGS. 9 to 13. In this embodiment, the flaps 56 a and 56 b areconstructed to allow an airflow of approximately 0.1 to 0.2 liters andthen close automatically. In this example, the flaps 56 a and 56 b areoperated by servo motors 59 and the closing point can be time dependentor dependent on the volume of airflow. During the initial airflow(indicated by airflow arrows A in FIG. 16) the bypass inlets 57 will beclosed by flaps 56 b, i.e. flaps 56 a and 56 b will be in the verticalposition shown so that there will be no airflow B. When the flaps 56 aand 56 b close (i.e. they sit in a substantially horizontal position),air will then flow through the bypass inlets 57 (indicated by airflowarrows B in FIG. 16). Typically, the flaps 56 will be set to close andshut off airflow A when the volume of air which has been inhaled throughthe suction tube 41 is sufficient to remove the entire contents of acavity 53. At this point, the air which is inhaled no longer needs to bedried and accordingly, the air can enter the housing 44 via the bypassinlets 57. An advantage of the third and fourth embodiments over theembodiments depicted in FIGS. 1 to 8 is that the volume of drying agent43 can be reduced since less drying is needed if the flaps 56 closeautomatically.

A fifth preferred embodiment is depicted in FIGS. 17 to 21 and differsfrom the previous embodiments in that the drying agent is located in theblister pack. The inhalation device comprises a suction tube 61 and ablister pack 62 with a drying agent 63 located inside the blister pack62. The housing for directing air to the air inlet at the distal end 68of the suction tube 61 comprises a skirt 64 a extending downwardly atthe distal end 68 of the suction tube 61 and a blister pack holder 64 bin which the blister pack 62 sits.

In this embodiment, the suction tube 61 has an enlarged mouthpiece 69 inthe form of a collar 61 a through which bypass channels 77 are formed.The purpose of the bypass channels 77 is to ease the effort required bythe user to inhale. Clearly, some air will enter the bypass channels 77rather than through the blister pack holder 64 b. Often, it is theinitial airflow which determines the quality of the inhalation of thepowdered medicament.

The blister pack 62 comprises one or more blisters 65, each of whichwill be provided with a separate block of drying agent 63. The blisterpack 62 comprises a lower base 71 and an upper foil layer 72. The lowerbase 71 holds one or more cavities 73 and also forms an enclosure aroundthe drying agent 63. The lower base 71 is provided with upper annularchannels 66 and lower annular channels 67 which help to direct theairflow through the blister pack 62. A lower foil layer 74 seals theblister pack 62 until the inhalation device is ready for use.

In use, the blister pack 62 is first pushed into the blister pack holder64 b. At this point lower foil layer 74 is broken by the upstandingwalls 75 which sit in annular channels 67 and form the entrance for airinto the blister pack 62. The suction tube 61 should then be pushed intothe blister pack 62 by breaking the upper foil layer 72. At the end ofthe skirt 64 a are depending walls 76 which will sit inside the annularchannels 66. Reference should now be made to FIG. 21 which includesairflow arrows showing how moist air is drawn in through the blisterpack holder 64 b, up through the drying agent 63, where drying occurs,and then into annular channels 66 before entering the interior volume ofskirt 64 a subsequently being drawn into cavity 73, up through the airinlet 68 of the suction tube 61, into air passage 70 and to themouthpiece 69.

FIGS. 22 to 26 depict a sixth preferred embodiment which is similar tothe sixth embodiment in that the drying agent is also located in theblister pack. However, the airflow enters the blister pack from aboverather than from below. The inhalation device comprises a suction tube81 and a blister pack 82 which holds the drying agent 83. The dryingagent 83 is in the form of a block which is shaped to sit below a cavity93 in the blister pack 82. The blister pack 82 is provided with twopart-annular channels 86 a and 86 b which help to direct the airflowthrough the blister pack 82. The suction tube 81 has a distal end 88which forms the air inlet and a proximal end 89 which forms the airoutlet or mouthpiece. The distal end 88 of the suction tube 81 includesa skirt 84 which acts as a housing for directing air to the air inlet.The skirt 84 includes a part-annular inlet channel 87 a which will sitinside annual channel 86 a when the suction tube 81 is pushed into theblister pack 82.

The blister pack 82 comprises one or more blisters 85, each of whichwill be provided with a separate block of drying agent 83. The blisterpack has a lower base 91 and an upper foil layer 92. The lower base 91holds one or more cavities 93 and also forms an enclosure for dryingagent 83.

In use, the user will push the suction tube 81 into the blister pack 82and the distal end 88 will penetrate the foil layer 92. When the userinhales, moist air will be drawn into annular channel 87 a (see FIG. 25with airflow arrows). The air will then pass into the blister pack 82through annular channel 86 a and into the drying agent 83. The air willbe dried as it passes through the drying agent 83, eventuallyre-entering the volume 87 b within skirt 84 of the suction tube 81. Theair then passes down through the broken foil layer 92 and into cavity 93lifting the powder formulation up into air passage 90 and to themouthpiece 89. FIG. 26 is a view from below of the suction tube 81,depicting the annular channel 87 a, the volume 87 b and the distal end88 forming the air inlet.

This embodiment is more compact than the fifth embodiment depicted inFIGS. 17 to 21 and will avoid the user covering the air intake with thehands since the hands do not need to touch the skirt 84. In contrast, inFIG. 17, it is clear that the user could inadvertently block the airintake in the blister pack holder 64 b. However, the fifth embodimentwill permit a larger airflow through the inhalation device.

A seventh embodiment is depicted in FIGS. 27 to 31 in which the dryingagent is also located in the blister pack. The inhalation devicecomprises a suction tube 101 and a blister pack 102 which holds thedrying agent 103. The drying agent 103 is in the form of a flexible tubewhich can be placed in a cavity 106 in the blister pack 102. The tube ofdrying agent 103 is constructed such that it will sit substantiallylevel with the top surface of the blister pack 102. The suction tube 101has a distal end 108 which forms the air inlet and a proximal end 109which forms the air outlet or mouthpiece. At the distal end 108 thesuction tube 101 has a skirt. 104 which acts as a housing to direct airto the air inlet 108.

The blister pack 102 comprises one or more blisters 105 each of which isprovided with a separate block of drying agent 103. The blister pack 102has a lower base 111 and an upper foil layer 112 a/112 b. The lower base111 holds one or more cavities 113 and also forms an enclosure for thedrying agent 103 in the form of cavity 106.

In use, the user peels off a first annular foil piece 112 a and thenpushes the suction tube 101 into the blister pack 102. Reference shouldnow be made to FIG. 30 which includes airflow arrows. The penetration ofthe blister pack 102 by the suction tube 101 pierces a second circularfoil piece 112 b. The moist air will flow into the cavity 106 whichholds the drying agent 103 where it is dried and will then pass up intothe volume within the skirt 104 of the suction tube 101. Subsequently,the air will flow down into cavity 113 and up into air passage 110 tothe mouthpiece 109.

Alternatively, a single foil layer 112 could be used but a disadvantagewith peeling off a single foil layer 112 before penetration of thecavity 113 is that the contents of the cavity 113 and the drying agent103 would be exposed to moist air even before the suction tube 101penetrated the cavity 113. Therefore, the arrangement of two foil pieces112 a/112 b rather than a single foil layer is preferred. The first foilpiece 112 a exposes only the drying agent 103 and would be manuallyremoved whereas the second foil piece 112 b would be penetrated by thedistal end 108 on entering cavity 113. In this way, the powderformulation in cavity 113 would not be affected by moist air.

An eighth preferred embodiment is depicted in FIGS. 32 to 35 which issimilar to the seventh embodiment. The aim of this embodiment is to useonly a single foil layer which is removed simply by pushing the suctiontube 121 into the blister pack 122. The main distinguishing feature arethe protrusions 127 which extend below skirt 124 on the suction tube121. In addition, the cavity 126 in blister pack 122 has been modifiedsuch that it sits above the level of the cavity 133 which holds thepowder formulation. The drying agent 123 is in a similar tubular formand sits in cavity 126. A single foil layer 132 covers the blister 125which can be penetrated by the distal end 128 of the suction tube 121.Preferably, the foil layer 132 is perforated at point “P”in the regionof the outer radius of the drying agent 123. When the suction tube 121is pushed into the blister pack 122 the distal end 128 will break thefoil 132 but the protrusions 127 will ensure that the foil layer 132 ispushed downwards to clear an airflow passage.

The protrusions 127 will serve to push the foil layer 132 at the Innerdiameter of the drying agent 123 which results in tearing of the foillayer 132 at the perforations P near the outer diameter of the dryingagent 123. In this way, air will be able to flow into the cavity 126 andthrough the drying agent 123. Airflow arrows are included in FIG. 35where it is clear that the air will flow down into the cavity 133 and upthrough air passage 130 to the mouthpiece 129. In this case, the skirt124 sits flush against the blister pack 122. Optionally, the cavity 133could include an additional foil layer to prevent the drying agent 123from coming into contact with the powder formulation.

The ninth embodiment of the present invention is depicted in FIGS. 36 to39 and is a variation on the eighth embodiment with the drying agentlocated above the blister in the blister pack. The inhalation devicecomprises a suction tube 141 and a blister pack 142. A housing 144 sitsabove the blister pack 142 and holds an annular block of drying agent143. The drying agent 143 is sealed within housing 144 by a foil layer147. An annular divider 146 is secured to the lower face of the dryingagent 143. The blister pack 142 comprises a lower base 151 having one ormore cavities 153 and an upper foil layer 152 which seals in the powderformulation within the cavity or cavities 153.

In use, the distal end 148 of the suction tube 141 is pushed throughfoil layer 143. The flange 154 on the suction tube 141 will eventuallycome to rest against the annular divider 146 (see FIG. 39). At thispoint, the cutting mechanism on the suction tube 141 will have cut thefoil layer 152 and penetrated cavity 153. Air will be drawn in as shownin FIG. 39. Since the flange 154 sits tightly against divider 146, aircannot flow directly into the cavity 153 but will have to flow throughthe drying agent 143. The foil layer 147 protects the drying agent 143whereas the foil layer 152 protects the contents of the blister 145. Inaddition, the housing 144 should be virtually impenetrable by moisturein the surrounding air. The foil layer 152 could be made permeable inorder to allow the drying agent 143 to keep the powder formulation inthe blister 145 dry during storage.

FIG. 40 depicts a modified embodiment of the applicants' inhalationdevice known as the TURBUHALER® which comprises a drying agent in thelower or distal end. The inhalation device operates substantially in themanner described in WO 98/41256 and differs in that a block of dryingagent is located adjacent to the main air inlet which is now in thedistal end rather than in the side of the device. The drying agent driesthe air drawn by a user into the inhalation device prior to contact withthe powdered medicament in the dosing means. The components of theinhalation device will only be described briefly since a fulldescription is available by reference to WO 98/41256.

The inhalation device comprises a suction tube 151 having a distal end158 and a proximal end 159. The user primes the inhalation device foruse by rotating a gripping portion 160 which moves a dosing means 161 inthe form of a plate such that a dose of powdered medicament sits in theair passage 162 passing between the distal and proximal ends 158,159 ofthe inhalation device. When the user inhales from the proximal end 159,air will be drawn through the distal end 158 via main air inlet 152,through the drying agent 153 and up into air passage 162 entraining thedose of powdered medicament in the dried stream of air. The powder thenpasses through a helical passage 163 and leaves the inhalation devicevia air outlet 154 into the mouth of the user. Although desiccants havebeen used in this type of inhalation device for drying the powderedmedicament, a drying agent has never been used for reducing humidity inthe air drawn into the inhalation device.

A further embodiment of the present invention is depicted in FIGS. 41 to44. This is a modification of the applicants' inhalation device known asthe MONOHALER® described in WO 92/04069. The inhalation device comprisesa suction tube 171 having a distal end 178 and a proximal end 179. Thedistal end 178 comprises the air inlet 172 and the proximal end 179which forms the mouthpiece comprises an air outlet 174. The inhalationdevice further comprises a drying agent 173 located inside the suctiontube 171 just inside the air inlet 172. A single dose of powderedmedicament 177 in a cavity 180 is sealed by lower foil strip 175 andupper foil strip 176 in an airtight way until the user wishes to inhalethe powder. The foil strips 175 and 176 are simply pulled away from thedistal end 178 (foil strip 176 passing through a hole 182) and thepowder 177 is then exposed and can be inhaled when the user breathes infrom the proximal end 179. Airflow arrows are included in FIGS. 43 and44. FIG. 44 is an enlarged view of the distal end 178 of the inhalationdevice in FIG. 43. Details of the lower and upper foil strips 175, 176can be seen. When these strips are removed air can flow into theinhalation device both above and below the powdered medicament 177. Theairflow A below the powdered medicament 177 is introduced to easerelease of the powder into the airflow B which has been dried on passingthrough the drying agent 173. The volume of airflow A is minimal incomparison to the volume of airflow B and is, therefore, not significantwith regard to any contact it makes with the powdered medicament 177when passing through a small hole 181 in the bottom of cavity 180.Drying of airflow A is not necessary since the main objective of thisairflow is to prevent vacuum effects holding the powdered medicament 177in the cavity 180. However, a further block of drying agent could belocated in airflow A if a detrimental effect were to occur. Thereafter,the powder travels with the airflow through the suction tube 171 to theair outlet 179 into the mouth of the user. The specific design of asuction tube similar to suction tube 171 is described in detail in WO92/04069 although the design in this embodiment has been modifiedslightly.

1. An inhalation device for delivery of a powdered medicament comprisinga suction channel and a plurality of doses of powdered medicament, thesuction channel having a distal end and a proximal end with an airpassage therethrough, the distal end having an air inlet and theproximal end having an air outlet which forms a mouthpiece of thedevice, wherein the inhalation device further comprises a means fordrying air drawn by a user into the inhalation device prior to contactwith the powdered medicament such that a dose of powdered medicamentwill be dispersed in dried air for delivery at the proximal end, whereinthe means for drying air is located outside the suction channel suchthat air is dried prior to entering the air inlet and a means formetered dosing of the powdered medicament, wherein the means for dosingis configured to meter a predetermined amount of powdered medicament perdose, independent of the air flow drawn into the inhalation device bythe user.
 2. An inhalation device as claimed in claim 1, wherein atleast part of the volume of the air drawn by the user into theinhalation device passes through the means for drying the air prior tocontact with the powdered medicament.
 3. An inhalation device as claimedin claim 1, wherein the suction channel is in the form of a suction tubeand the powdered medicament is located outside the suction tube.
 4. Aninhalation device as claimed in claim 3, wherein the powdered medicamentis contained in a blister pack having one or more blisters and thesuction tube is constructed such that the distal end can penetrate ablister.
 5. An inhalation device as claimed in claim 4, wherein theinhalation device further comprises a housing having one or morechannels therein for directing air inhaled by the user to the air inlet.6. An inhalation device as claimed in claim 5, wherein the means fordrying the air is located between the housing and the air inlet.
 7. Aninhalation device as claimed in claim 3 wherein the means for drying airincludes a drying box in fluid communication with the suction tube viaan elongated conduit.
 8. An inhalation device as claimed in claim 7wherein the conduit includes a valve constructed to prevent airflow fromthe suction tube into the drying box.
 9. An inhalation device as claimedin claim 3 wherein the means for drying air surrounds the suction tube.10. An inhalation device as claimed in claim 1 wherein the means fordrying air comprises a drying agent disposed in a container with thepowdered medicament.
 11. An inhalation device as claimed in claim 1wherein the means for drying air includes an air intake, and means forsealing the air intake when the device is not in use.
 12. An inhalationdevice as claimed in claim 11 wherein the means for sealing isconstructed to seal the air intake after inhalation is complete or aftera predetermined time or predetermined volume of airflow.
 13. Aninhalation device as claimed in claim 11 wherein the device includes abypass intake, not in fluid communication with the means for drying air,that remains open after the air intake is sealed.
 14. An inhalationdevice as claimed in claim 11 wherein the means for sealing includeshinged flaps.
 15. An inhalation device as claimed in claim 14 whereinthe flaps are operated by a motor.
 16. An inhalation device as claimedin claim 1 wherein the powdered medicament is separated from the dryingmeans by a seal.
 17. An inhalation device for delivery of a powderedmedicament comprising a suction channel and one or more doses ofpowdered medicament, the suction channel having a distal end and aproximal end with an air passage therethrough, the distal end having anair inlet and the proximal end having an air outlet which forms amouthpiece of the device, a means for drying air drawn by a user intothe inhalation device prior to contact with the powdered medicament suchthat a dose of powdered medicament will be dispersed in dried air fordelivery at the proximal end, and a means for metered dosing of thepowdered medicament, wherein the means for dosing is configured to metera predetermined amount of powdered medicament per dose, independent ofthe air flow drawn into the inhalation device by the user, and whereinthe suction channel includes a suction tube, and the powdered medicamentis located outside the suction tube.
 18. An inhalation device fordelivery of a powdered medicament comprising a suction channel and oneor more doses of powdered medicament, the suction channel having adistal end and a proximal end with an air passage therethrough, thedistal end having an air inlet and the proximal end having an air outletwhich forms the mouthpiece of the device, a means for drying air drawnby a user into the inhalation device prior to contact with theaggregated powdered medicament such that a dose of powdered medicamentwill be dispersed in dried air for delivery at the proximal end, and ameans for metered dosing of the powdered medicament, wherein the meansfor dosing is configured to meter a predetermined amount of powderedmedicament per dose, independent of the air flow drawn into theinhalation device by the user.
 19. An inhalation device for delivery ofa powdered medicament comprising a suction channel and one or more dosesof powdered medicament, the suction channel having a distal end and aproximal end with an air passage therethrough, the distal end having anair inlet and the proximal end having an air outlet which forms amouthpiece of the device, a means for drying air drawn by a user intothe inhalation device prior to contact with the powdered medicament suchthat a dose of powdered medicament will be dispersed in dried air fordelivery at the proximal end, a means for metered dosing of the powderedmedicament, wherein the means for dosing is configured to meter apredetermined amount of powdered medicament per dose, independent of theair flow drawn into the inhalation device by the user, and a bypasswhereby some of the air drawn into the inhalation device by the user isallowed to bypass the means for drying air.